JP2017516086A - A rotatable cartridge for measuring properties of biological samples - Google Patents

Abstract

The present invention provides a cartridge (100, 200, 2100) formed from a carrier structure (118) and a cover (400) for an automated analyzer (2200). At least one container (106) comprising at least one fluid reservoir (108, 202), wherein the cartridge is operable to rotate about an axis of rotation (102) and includes at least one fluid (110, 204); Have. Each container is configured to rotate relative to the cartridge about the axis of rotation within the cavities (104, 104 '), wherein at least one cavity is formed between the carrier structure and the cover. Each fluid reservoir comprises a pierceable seal (112) and the cavity comprises a piercing structure (114) for each fluid reservoir. The piercing structure is configured to open the seal when the container is rotated relative to the cartridge. Each container has a first friction element (412) and each cavity has a second friction element (414) that mates and causes friction. Each container comprises a first engagement surface (406) operable to mate with a second engagement surface (408) of a rotary actuator operable to apply torque to the container. . The cartridge has a fluid structure (120, 2116, 2117, 2118, 2120, 2121, 2122, 2123, 2124, 2125, 2130, 2131, 2132, 2133, 2134) for processing the biological sample into a processed biological sample. 2135). There is a duct (116) between the cavity and the fluid structure. A measurement structure (2219, 2210) is provided to allow the fluid structure to measure the treated biological sample. [Selection] Figure 1

Description

  The present invention relates to analytical test devices for biological samples, and in particular to the design and use of a rotatable cartridge for performing biological sample measurements.

  In the field of medical analysis, two types of analysis systems are known: wet analysis systems and dry chemical analysis systems. In essence, a wet analysis system that operates using “wet reagents” (liquid reagents) performs the analysis through a number of necessary steps, eg, samples and reagents. Measure the mixture for the characteristics of the measurement variables for the purpose of providing in the reagent container, mixing the sample and reagent together in the reagent container, and obtaining the desired analytical result (analysis result) To analyze. These steps are often performed using technically complex, large, line-operated analytical instruments that allow the required wide variety of movement of the involved elements. This type of analysis system is typically used in large medical analysis laboratories.

  On the other hand, dry chemical analysis systems typically operate using a “dry reagent” that is integrated within the test element and implemented, for example, as a “test strip”. When these dry chemical analysis systems are used, the liquid sample dissolves the reagent in the test element, and the measurement variable changes due to the reaction of the sample with the dissolved reagent, which can be measured by the test element itself. In particular, analytical systems that can be analyzed optically (specifically colorimetric analysis) are typical of this type of analytical system, where the measurement variable is a color change or other optically measurable Is a variable. Electrochemical systems are also typical in this type of analytical system, where the characteristic of an electrical measurement variable for analysis, specifically the current when a given voltage is applied, is measured. It can be measured in the measurement zone of the test element using electrodes provided in the zone.

  Analytical instruments for dry scientific analysis systems are usually compact, some of which are portable and battery powered. These systems are used for distributed analysis, for example, at the office worker, in the hospital room, and by monitoring the patient's own medical analysis parameters (especially blood glucose analysis by diabetic patients or coagulation status by warfarin patients). Used in so-called "home monitoring".

  In the wet analysis system, it is possible to perform a more complicated multi-step reaction sequence (test protocol) by using a high-performance analytical instrument. For example, immunochemical analysis often requires a multi-step reaction sequence, where “bound / free separation” (hereinafter “b / f separation”), ie separation of bound and free phases Necessary. According to one test protocol, for example, a probe can first be transported through a porous solid matrix containing a specific binding reagent for an analyte. A marking reagent can then be allowed to flow through the porous matrix, thereby labeling the bound analyte and allowing its detection. In order to achieve an accurate analysis, a washing step must be performed in advance, where unbound marker-adding reagent is completely removed. Many test protocols are known for determining a wide variety of analytes, which differ in a wide variety of ways but have the common feature of requiring complex handling involving multi-step reaction steps. Also, this may specifically require b / f separation.

  Test strips and similar analytical elements typically do not allow a controlled multi-step reaction sequence. Test elements similar to test strips are known and allow for other functions such as separating red blood cells from whole blood in addition to supplying reagents in dry form. However, they usually do not allow precise control of the time sequence of the individual reaction steps. Wet chemical laboratory systems provide these capabilities, but are large and expensive, and are too complex to handle for many applications.

  In order to fill such gaps, it is implemented in such a way that at least one liquid transport step that is controlled from the outside (ie using an element outside the test element itself) is carried out therein. Analysis systems have been proposed that operate using test elements ("controllable test elements"). Such external control can be applied by applying a pressure difference (excessive pressure or low pressure), or changing the action of force (for example, changing the action direction of gravity by changing the posture of the test element or accelerating force). ). Such external control is carried out particularly frequently by centrifugal forces acting on the rotating test element as a function of the rotational speed.

  Analytical systems with controllable test elements are known, which usually have a housing containing a dimensionally stable plastic material and a sample analysis channel surrounded by the housing, and the sample analysis channel is often A series of channel sections and a chamber positioned therebetween, which is wider compared to the channel sections. The structure of the sample analysis channel with its channel section and chamber is defined by building the outline of the plastic part. Creating the contour in this way can be done by injection molding techniques or hot stamping. Recently, however, microstructures made by lithographic techniques are increasingly used.

  Analytical systems with controllable test elements can miniaturize tests that could only be performed using a large laboratory system. In addition, they make it possible to parallelize the procedure by repeatedly applying the same structure for parallel processing of similar analyzes from one sample and / or the same analysis from different samples. A further advantage is that the test element can be normally manufactured using established manufacturing techniques and that the test element can be further measured and analyzed using known analytical methods. Known methods and products may be employed for the chemical and biochemical components of such test elements.

  Despite these advantages, further improvements are needed. In particular, analytical systems that operate using controllable test elements are still excessively large. Making the dimensions as compact as possible has a high practical significance in many intended applications.

  US Pat. No. 8,114,351 (B2) discloses an analysis system for analyzing a body fluid sample as an analyte. The analysis system provides a test element and an analytical instrument having a dosing station and a measurement station. The test element has a housing and (at least) one sample analysis channel surrounded by the housing. The test element can rotate about an axis of rotation extending through the test element.

  US Pat. No. 8,470,588 (B2) discloses a test element and method for detecting an analyte. The test element is essentially disk-shaped, flat and can be rotated about a central axis which is preferably perpendicular to the plane of the disk-shaped test element.

  Kim, Tae-Hyong et al., “Flow-enhanced electrochemical immunosensors on centrifugal microfluidic platforms”, Lab on a Chip 13.18 (2013), 3747-3c, i. Fully integrated centrifugal micro with features for capturing target antigens from biological samples via bead-based enzyme-linked immunosorbent assays and for flow-enhanced electrochemical detection A fluidic device is disclosed. This is integrated into a centrifugal microfluidic disc, also known as “lab-on-disc” or microfluidic CD.

  Martinez-Duarte, Rodrigo et al., "The integration of 3D carbon-electrode dielectrophoresis on a CD-like centrifugal microfluidic platform, 0. In the following, “Martinez-Duarte et al.”) Discloses a dielectrophoresis-assisted filter with a compact disc (CD) -based centrifuge platform. A three-dimensional carbon electrode is fabricated using C-MEMS technology and is used to implement a dielectrophoretic active filter (DEP-enabled active filter) for capturing particles of interest.

International patent application WO2014 / 041364 is
At least one capillary passage comprising a first inlet and an outlet for receiving a sample;
A side passage extending partly from the capillary passage along the length of the capillary passage and leading to the outlet;
A second inlet located between the first inlet and the intersection of the side passages;
A sample metering device for a liquid sample is disclosed. A fluid application region for receiving a fluid sample to be tested is provided for entering the capillary passage through the first inlet, and a second fluid application region for introducing fluid, such as a case buffer, into the capillary passage. Provided for. The second inlet prevents any sample in the well from entering the capillary passage too much when the case buffer is added.

US Patent Application Publication No. 2013/0344617 (A1)
At least one capillary passage comprising an inlet and an outlet;
A side passage extending partly from the capillary passage along the length of the capillary passage and leading to the outlet;
A fluid application area for receiving a liquid sample to be tested and entering the capillary passage through the inlet;
A first sealing means capable of sealing the outlet of the capillary passage and operating releasably;
A second sealing means that seals the outlet of the side passage and is operable releasably;
A sample metering device for a liquid sample is disclosed.

  US 2012/0291538 (A1) discloses a system and method for volumetric metering in a sample processing device. A waste reservoir disposed in fluid communication with a first end of the metering reservoir for catching excess liquid from the metering reservoir that exceeds a selected volume; Can have. The system can further include a capillary valve in fluid communication with the second end of the metering reservoir to inhibit liquid from exiting the metering reservoir until desired. The method measures the liquid by rotating the sample processing device to exert a first force on the liquid that is insufficient to move the liquid into the capillary valve; Rotating the sample processing device to exert a second force on the liquid that exceeds the first force for the purpose of moving the liquid to the processing chamber via a capillary valve.

US Patent Application Publication No. 2004/011686 (A1) maintains high frequency of contact between nucleic acid and solid phase in sample during nucleic acid capture process for the purpose of increasing capture rate, easy to automate A nucleic acid purification apparatus is disclosed, and the nucleic acid purification apparatus is
Means for separating the liquid containing the nucleic acid therein from the sample via centrifugal force;
Means for transferring the reagent via centrifugal force;
Means for making a mixed liquid of the reagent transferred via centrifugal force and the solution containing the nucleic acid therein;
A carrier for capturing the nucleic acid;
Means for transferring the mixed liquid to the carrier via centrifugal force;
Heating means for heating the carrier;
Holding means for separating and holding the reagent containing the nucleic acid eluted from the carrier;
Is provided.

U.S. Pat. No. 8,114,351 (B2) US Patent No. 8,470,588 (B2) International patent application WO2014 / 041364 US Patent Application Publication No. 2013/0344617 (A1) US Patent Application Publication No. 2012/0291538 (A1) US Patent Application Publication No. 2004/011686 (A1)

Kim et al., “Flow-enhanced electrochemical immunosensors on centrifugal microfluidic platforms”, Lab on a Chip 13.18 (2013), pages 3747-3754, doi: 10.10337 / cl3 Martinez-Duarte et al., “The integration of 3D carbon-electrode dielectrophoresis on a CD-like centrifugal microfluidic platform”, 10 pp. 1043, Lab.

  The invention provides a method for performing measurements, a cartridge for an automatic analyzer, and an automatic analyzer within the independent claims. Embodiments are given in the dependent claims. This measurement can be, for example, an optical measurement or an electrical measurement.

In one aspect, the present invention provides a method for performing a measurement of a processed biological sample using a cartridge.
As used herein, a cartridge includes a test element for processing a biological sample into a processed biological sample. The cartridge can have a structure or component that allows a measurement to be performed on a biological sample. The cartridge is a test element as defined and described in US Pat. No. 8,114,351 (B2) and US Pat. No. 8,470,588 (B2). The cartridges used herein may also be referred to as centrifugal microfluidic discs, also known as “lab-on-discs” or microfluidic CDs.

As used herein, biological samples include chemical products that are extracted, copied, replicated, or regenerated from a sample taken from an organism.
The cartridge is operable to rotate about an axis of rotation. The cartridge further comprises at least one container comprising at least one fluid reservoir containing at least one fluid. In some embodiments, the cartridge can have more than one container. In some embodiments, each container can have one fluid reservoir, and in other embodiments, each container can have more than one fluid reservoir. Each of the different fluid reservoirs in the same cartridge can contain the same fluid, or one or more of these reservoirs can contain a different fluid. The cartridge includes a cavity for each of the at least one container. The cartridge can also comprise at least a common cavity for two or more containers. At least one container is configured to rotate about the axis of rotation of the cartridge within the cavity. In some embodiments, the axis of rotation passes through the cavity. In this case, the container rotates about this axis just inside the cavity. In other embodiments, the axis of rotation is outside the cavity. In this case, a particular container is constrained to move within the cavity to rotate about the axis of rotation.

  At least one container is configured to rotate relative to the cartridge. Each of the at least one fluid reservoir includes a pierceable seal. A pierceable seal seals each fluid reservoir so that no fluid exits. Perforating a pierceable seal allows fluid to exit a particular fluid reservoir. The cavity comprises at least one perforation structure for each of the at least one fluid reservoir. At least one piercing structure is configured to open the seal by piercing the pierceable seal when the at least one container is rotated relative to the cartridge. Each container is in a cavity. Each cavity can comprise one container or multiple containers. In the latter case, multiple containers share a common cavity. Within each cavity is a piercing structure for each pierceable seal. By rotating a specific container relative to the cartridge about the axis of rotation, the specific container moves to a position where a pierceable seal is pierced by the piercing structure for the purpose of opening a specific fluid reservoir. It will be.

  At least one container comprises a first friction element and the cavity comprises a second friction element. The first friction element mates with the second friction element. The first friction element and the second friction element are configured to cause friction between the cavity and the at least one container. The first and second friction elements cause friction that prevents the particular container from rotating when the particular container should not rotate about the axis of rotation. At least one container comprises a first engagement surface operable to mate with a second engagement surface of a rotary actuator operable to apply torque to the at least one container. A rotary actuator is used to intentionally move the container relative to the cartridge in a controlled manner so that the piercing structure contacts the pierceable seal. This relative movement is intended to bring the piercing structure into contact with the pierceable seal by using a rotary actuator to fix the container and rotating the cartridge for the purpose of bringing the piercing structure into contact with the pierceable seal or The container at a rotational speed different from that of the cartridge, using the rotary actuator for the purpose of fixing the cartridge as a rotating container using a rotary actuator, or for the purpose of bringing the piercing structure into contact with the pierceable seal Can be achieved by rotating.

  The cartridge further comprises a fluidic structure for processing the biological sample into a processed biological sample. For example, the cartridge can include an inlet or location (sample port) that allows a biological sample to be placed into the cartridge and reach the fluidic structure. The cartridge further comprises a duct between the cavity and the fluid structure. A duct may allow fluid originally stored in the fluid reservoir to leave the cavity and enter the fluid structure. The duct can be implemented in several different ways. For example, the cavity may be closer to the axis of rotation than the fluid structure. The cartridge can then be rotated to allow fluid to pass through the duct and enter the fluid structure. In other cases, the fluid reservoir can empty the fluid and enter the cavity, where the siphon causes the fluid to enter the fluid structure.

The fluid structure comprises a structure for allowing the treated biological sample to be measured. The fluid structure is configured to receive a biological sample.
The method includes placing a biological sample in the fluid structure. The method rotates the at least one container about the axis of rotation of the cartridge relative to the cartridge so as to overcome friction between the cavity and the at least one container and to open the pierceable seal And further applying a torque to the at least one container using a rotary actuator. Rotating at least one container relative to the cartridge causes at least one piercing structure to open the seal by piercing the pierceable seal.

  The method further includes controlling the rotational speed of the cartridge for the purpose of processing the biological sample using the fluid structure into a processed biological sample. The method further includes controlling the rotational speed of the cartridge so that at least one fluid is passed through the duct and at least a portion of the fluid structure. When the rotary actuator is not engaged with the container, friction between the cavity and the at least one container causes the at least one container to rotate about the axis of rotation at the same speed as the cartridge.

  The method further includes performing the measurement by using the measurement structure and using the measurement system. Note that the first step of the method is to place the biological sample in the fluid structure and the last step is to perform the measurement. However, other steps of the present invention may be performed in a different order and various steps may be performed more than once. For example, a cartridge can have more than one container, and a particular container can have more than one fluid reservoir. In this way, torque can be applied to different containers at different times to release different fluids, and processed biological samples can be processed for different cartridges in different test plans. The particular order for the sample can occur in different forms.

  This embodiment can potentially have one or more of the following advantages listed in this paragraph: the container can be protected from mechanical damage (eg, in transit or in storage). The container can be protected from unwanted contact with the user (a relatively rigid cover prevents the container from being pushed by the user and thereby unintentionally opening the container). A fixed and non-exchangeable combination of container and disk can be provided. This can ensure the “compatibility” or usefulness of the reagents on the disk and in the reservoir. Furthermore, this makes it possible to improve the reliability of the test result (the user cannot change the container), that is, to improve the certainty that the test result can be appropriately obtained.

The fluid structure may be a microfluidic structure.
Measurements include, but are not limited to, photometric transmittance measurement, light scattering measurement, chemiluminescence, fluorescence emission, total internal reflection fluorescence (TIRF), and electrochemiluminescence (ECL) measurement, May be included.

  The pierceable seal can be a thin film or foil, for example. For example, a thin piece of metal foil or plastic film can be used as the pierceable seal. The piercing structure may be any structure capable of piercing a particular pierceable seal, which may be, for example, a pin, lance (lancet) or sharp edge.

  Each fluid reservoir can be filled with fluid. If there are multiple reservoirs within a particular cartridge, two or more fluid reservoirs can have the same fluid. However, different fluid reservoirs may have different fluids.

  As used herein, a rotary actuator is used and configured to apply torque to one or more containers within a cartridge to rotate the container relative to the cartridge about a rotational axis. Actuator. In some embodiments, the rotary actuator may be a device or apparatus that holds a particular container in a fixed position as the cartridge is rotated. In other embodiments, a rotary actuator may be installed on, for example, a clutch or other mechanism so that the rotary actuator rotates with the cartridge. In this case, the rotary actuator is further configured to further rotate the container relative to the cartridge when rotating with the cartridge.

  In another embodiment, the measurement structure is a transparent structure. The transparent structure may be a window, for example. The transparent structure may be optically transparent. In another embodiment, the transparent structure has two or more transparent and / or optical components. For example, on one side there may be a window on one side of the container and on the other side there may be a mirror. The optically transparent structure may be, for example, a hole on one or both sides of the cartridge. The transparent structure can further comprise an optical filter. The transparent structure may also include being transparent outside the visible range, such as near infrared or near ultraviolet. Optical measurements as used herein may also include measurements in the near infrared or near ultraviolet range. In other embodiments, being optically transparent may exclude the near infrared region or the near ultraviolet region.

  In other embodiments, the measurement structure comprises two or more electrodes for performing electrical or ECL measurements on the treated biological sample. For example, the measurement structure of Martinez-Duarte et al. Or Kim et al. Can be incorporated into the cartridge.

  The advantage of this method is that at least one fluid reservoir can be opened at a particular time before, during, and after processing the biological sample into a processed biological sample. The fluid may be released more than once, and more than one type of fluid may be used. This allows for a more flexible and complex method for processing a biological sample into a processed biological sample. This can further reduce the amount of instrumentation required to do this. For example, the use of a container within the cartridge can eliminate the need for using a dosing needle to dispense at least one fluid into the cartridge.

  In another aspect, the present invention provides a cartridge for an automated analyzer. The cartridge is operable to rotate about an axis of rotation. The cartridge further comprises at least one container comprising at least one fluid reservoir containing at least one fluid. The cartridge includes a cavity for each of the at least one container. At least one container is configured to rotate within the cavity about the axis of rotation of the cartridge. At least one container is configured to rotate relative to the cartridge. Each of the at least one fluid reservoir includes a pierceable seal. The cavity comprises at least one perforation structure for each of the at least one fluid reservoir. At least one piercing structure is configured to open the seal by piercing the pierceable seal when the at least one container is rotated relative to the cartridge.

  At least one container comprises a first friction element and the cavity comprises a second friction element. The first friction element mates with the second friction element. The first friction element and the second friction element are configured to cause friction between the cavity and the at least one container. At least one container comprises a first engagement surface operable to mate with a second engagement surface of a rotary actuator operable to apply torque to the at least one container. The cartridge includes a fluid structure for processing the biological sample into a processed biological sample. The cartridge includes a duct between the cavity and the fluid structure. The fluid structure optionally comprises a transparent structure to allow optical measurement of the treated biological sample. The fluid structure is configured to receive a biological sample.

  This cartridge and other cartridges described herein can have the advantage that at least one fluid can be provided into the fluid structure without the use of an external dosing needle or system.

  In another embodiment, the cartridge comprises a plurality of fluid reservoirs. This can be implemented in a variety of different ways. For example, the cartridge can have a single container with multiple fluid reservoirs. In another option, the cartridge comprises a plurality of containers with, for example, one fluid reservoir per container. In another option, there are a plurality of containers and one or more of the plurality of containers has two or more fluid reservoirs per container. This allows more complex processing to make a biological sample a processed biological sample because the same fluid can be provided more than once to the fluid structure or a variety of different fluids can be provided. Can be advantageous because of

  In another embodiment, the plurality of fluid reservoirs are operable to be opened at different angular positions of the at least one container relative to the cartridge. For example, if there are multiple reservoirs on the same container, different fluid reservoirs can be opened independently of each other by rotating the container to different angular positions.

  In another embodiment, at least one container has a plurality of surfaces. Seals for the plurality of chambers are distributed on two or more of the plurality of surfaces. For example, the reservoir may be located on both sides of the at least one container or on different sides.

  In another embodiment, the first friction element and the second friction element comprise any one of the following: a rough surface, a surface having adhesive properties, a series of protrusions, a matching sinusoidal surface, Press fit structure, separation structure, and ratchet structure. Using any of these structures or a combination of these structures has the advantage that the container can be prevented from rotating relative to the cartridge when not being held down by the actuator. . This reduces the likelihood that fluid in a particular fluid reservoir will be metered in error.

In another embodiment, one of the at least one container is a centrally located container. The rotating shaft passes through the container located at the center.
In another embodiment, the centrally located container cavity is cylindrical. The central cavity is cylindrically symmetric about the axis of rotation.

  In another embodiment, one or more of the at least one container is configured to slide within the cavity. One or more of the at least one container is configured to rotate about the rotational axis of the cartridge by sliding in the cavity.

For example, the container can rotate around a pivot point located on the rotation axis.
Even in an off-center variant, the container rotates about the axis of rotation of the cartridge, but this motion in this case is a sliding motion in the cavity, for example a circle around the axis of rotation of the cartridge. It is a sliding motion on the rail-like structure located on one section. It is also possible to install a central container on the rail.

In another embodiment, one or more of the at least one container comprises a guiding structure for guiding a sliding motion in the cavity.
In another embodiment, the guiding structure is any one of the following: a rail and / or a cavity wall.

  In another embodiment, the cartridge comprises a carrier structure and a cover or lid structure that forms a cavity. The carrier structure has a disk-like portion. The disc-shaped part has a circular shape. This circular profile has a center. The rotation axis passes through the center. A fluid structure may be located within the carrier structure. The cover may be a plastic structure that is thinner than the carrier structure. In some embodiments, the cover may also be disk-shaped with an axis that also passes through its center.

  In another embodiment, the cartridge comprises an opening. At least one container is operable to rotate relative to the cartridge through the opening. The opening exposes the first engagement surface. The first engagement surface and the second engagement surface are connected to mechanically mate. For example, the first engagement surface and the second engagement surface may be interlocking structures such as a hexagonal shape, or a triangular or square shape.

In some embodiments where the cartridge is in the central cavity, the axis of rotation may pass through the opening. The opening may be in the cover or carrier structure, for example.
The engagement surface may be, for example, a peg, a plurality of pegs, a pin, or a more complex mechanical structure that interlocks.

In another embodiment, the opening is sealed using a cover layer.
The cover layer can be removed, for example, before use. The cover layer may also be a thin foil or film that simply pierces or peels when at least one container is actuated / engaged by a mechanical actuator.

  In another embodiment, the first engagement surface and the second engagement surface are configured to magnetically mate. For example, a particular container can have a magnet or a ferromagnetic or other magnetic material attached to the container. A magnet can then be used to rotate the container relative to the cartridge about the axis of rotation without any direct physical contact. The rotary actuator can use, for example, a permanent magnet or an electromagnet.

  In another embodiment, the at least one fluid is any one of the following: a dispersion, a fluid containing nanoparticles, a fluid containing blood grouping reagents, a fluid containing immunological reagents, a fluid containing antibodies, Fluids containing enzymes, fluids containing one or more substrates for enzymatic reactions, fluids containing fluorescent molecules, fluids containing molecules for measuring immunochemical reactions, molecules for measuring nucleic acid reactions Fluids containing, recombinant proteins, fluids containing virus isolates, fluids containing viruses, fluids containing biological reagents, solvents, diluents, buffers, fluids containing proteins, fluids containing salts, cleaning agents, Fluids containing nucleic acids, fluids containing acids, fluids containing bases, aqueous solutions, non-aqueous solutions, and combinations thereof.

  Note that if a cartridge has more than one fluid reservoir, it can have the same fluid multiple times or any combination of different fluids.

In another embodiment, the at least one container is a plurality of containers.
In another embodiment, the cartridge is formed from a carrier structure and a cover.
In another embodiment, at least one cavity is formed between the carrier structure and the cover.

In another embodiment, the piercing structure is configured to pierce a pierceable seal that is perpendicular to the axis of rotation.
In another embodiment, the cavity has a first flat surface that is perpendicular to the axis of rotation, and the container has a second flat surface that is perpendicular to the axis of rotation.

In another embodiment, the at least one container is configured to rotate about the axis of rotation so that the first flat surface and the second flat surface maintain a constant distance.
In another embodiment, the first friction element is formed on a first flat surface and the second friction element is formed on a second flat surface.

In another embodiment, the first friction element and the second friction element are configured to remain in contact when the at least one container is rotated about the axis of rotation.
In another embodiment, the fluid structure is formed from a carrier structure and a cover.

In another embodiment, the duct is formed from a carrier structure and a cover.
In another embodiment, at least one perforated structure is formed from the carrier structure.
In another embodiment, the container is completely in the cover and carrier structure. For example, the carrier structure can have an outer diameter that is symmetrical about the axis of rotation. The container may be completely inside the outer diameter.

In another embodiment, the carrier structure is disk shaped.
In another embodiment, the cavity has a first flat surface and the container has a second flat surface.

  In another embodiment, the first friction element is formed on the first flat surface. A second friction element is formed on the second flat surface. The first friction element and the second friction element are configured to maintain contact when at least one container rotates about the axis of rotation.

In another embodiment, the first flat surface is perpendicular to the axis of rotation. The second flat surface is perpendicular to the axis of rotation.
In another embodiment, at least one container is constrained to rotate about the axis of rotation so that the first flat surface and the second flat surface maintain a constant distance.

In another embodiment, the piercing structure is configured to pierce a pierceable seal that is perpendicular to the axis of rotation.
In another embodiment, at least one container is constrained to allow only rotational motion about the rotational axis of the cartridge within the cavity.

  In another embodiment, at least one container comprises a side wall, and the side wall comprises a pierceable seal. The sidewall may in some embodiments be a surface that is parallel to the axis of rotation. In another example, the sidewall may be a curved surface having a point that is parallel to at least one axis of rotation.

In another embodiment, the pierceable seal and the axis of rotation form an acute angle.
Another aspect of the present invention provides an automatic analyzer configured to receive a cartridge according to an embodiment. The automatic analyzer includes a cartridge spinner, a rotary actuator, a measurement system, and a controller configured to control the automatic analyzer. The measurement system can be, for example, an optical measurement system or an electrical measurement system.

  A cartridge spinner is operable to receive the cartridge and to rotate the cartridge about the axis of rotation. The measurement system is operable to make measurements using the measurement structure. The controller is configured or programmed to have executable instructions for rotating at least one container relative to the cartridge for the purpose of opening a pierceable seal using a rotary actuator. The controller further has executable instructions for controlling the rotational speed of the cartridge for the purpose of processing the biological sample using the fluid structure by controlling the cartridge spinner into a processed biological sample. Configured or programmed to

  The controller is further configured or programmed to have executable instructions for controlling the rotational speed of the cartridge for the purpose of allowing at least one fluid to pass through at least a portion of the duct and fluid structure. When the rotary actuator is not engaged with the container, rotational friction rotates at least one container at the same speed as the cartridge. The controller is further configured or programmed to have executable instructions for performing measurements using the measurement structure and measurement system. There may be more than one rotary actuator. For example, if the cartridge has more than one container, a particular rotary actuator may be operable to rotate each of the containers relative to the cartridge, or one or more of the containers There may be more than one rotary actuator for. In some embodiments, the cartridge may be rotated to a different position relative to the rotary actuator so that the rotary actuator is engaged with another container.

  In another embodiment, the automatic analyzer is configured to hold at least one container in a fixed rotational position relative to the automatic analyzer using a rotary actuator while rotating the cartridge.

  In another embodiment, the automated analyzer is configured to rotate a rotary actuator with the cartridge. A rotary actuator is configured to rotate at least one container relative to the cartridge during rotation of the cartridge.

  It should be understood that one or more of the above-described embodiments may be combined, provided that the combined embodiments are not mutually exclusive.

  In the following embodiments, the invention will be described in more detail by way of example only with reference to the drawings.

It is a top view which shows the Example of a cartridge. It is a figure which shows another Example of a cartridge. FIG. 3 is a perspective view showing the cartridge of FIG. 2. FIG. 3 is a perspective sectional view showing the cartridge 200 of FIG. 2. FIG. 3 is a diagram showing a part of a method using the cartridge of FIG. 2. FIG. 3 is another diagram illustrating a part of a method of using the cartridge of FIG. 2. FIG. 3 is another diagram illustrating a part of a method of using the cartridge of FIG. 2. FIG. 3 is another diagram illustrating a part of a method of using the cartridge of FIG. 2. FIG. 3 is another diagram illustrating a part of a method of using the cartridge of FIG. 2. FIG. 3 is another diagram illustrating a part of a method of using the cartridge of FIG. 2. FIG. 3 is another diagram illustrating a part of a method of using the cartridge of FIG. 2. It is a figure which shows the alternative design structure of a cartridge. FIG. 3 illustrates an alternative design configuration for a cartridge similar to the cartridge of FIG. It is sectional drawing which shows the cartridge of FIG. It is a figure which shows a part of cartridge provided with the container remove | deviated from the rotating shaft. It is a figure which shows a movement of a container provided with the cartridge of FIG. FIG. 16 is another view showing movement of a container including the cartridge of FIG. 15. FIG. 6 shows an alternative part of a cartridge with a container off the axis of rotation. FIG. 6 shows another embodiment of a portion of a cartridge that includes a container off the axis of rotation. It is a figure which shows one Example of a cartridge provided with the container 106 remove | deviated from the rotating shaft. FIG. 16 shows an example of a cartridge incorporating the container and cavity of FIG. It is a figure which shows one Example of an automatic analyzer. FIG. 23 is a flowchart illustrating a method for operating the automatic analyzer of FIG. 22.

  Elements denoted by the same reference numerals in these drawings are equivalent elements or perform the same function. The elements discussed above are not necessarily considered in the following figure if their functions are equivalent.

  FIG. 1 shows a top view of an embodiment of the cartridge 100. Not all components of this cartridge are shown. The cartridge 100 has a rotation shaft, that is, a rotation shaft 102. The center position and rotation axis of the cartridge 100 is indicated by x with 102. The cartridge 100 has a central cavity 104. Within the central cavity 104 is a container 106 having a fluid reservoir 108 that is filled with a fluid 110. One side of the container 106 is sealed with a pierceable seal 112. There are a plurality of piercing elements 114 in the central cavity 104. The container 106 is operable or configured to pivot or rotate about the axis of rotation 102. By rotating the container 106 about the rotation shaft 102, the pierceable seal 112 is pressed against the piercing element 114. When these occur, the piercing element ruptures and punctures the pierceable seal 112, thereby allowing the fluid 110 in the fluid reservoir 108 to escape and enter the central cavity 104. There is a duct 116 that connects the central cavity 104 to the body or carrier structure 118 of the cartridge 100. A space 120 exists where fluid structures for processing the biological sample into a processed biological sample can be placed so that measurements can be performed.

  FIG. 2 shows another embodiment of the cartridge 200. The embodiment shown in FIG. 2 is similar to the embodiment shown in FIG. 1 except that the container 106 has a first fluid reservoir 108 and a second fluid reservoir 202. The first reservoir 108 is filled with a fluid 110 and the second reservoir 202 is filled with a second fluid 204. In some cases, fluids 110 and 204 are the same fluid, and in other cases they are different. In this embodiment, there is a pierceable seal 112 that individually seals each of the fluid reservoirs 108, 202. By rotating the container 106 clockwise, the piercing element 114 opens the first fluid reservoir 108. By rotating the container 106 counterclockwise, the second fluid reservoir 202 is opened. In both the embodiments shown in FIGS. 1 and 2, the cartridges 100, 200 can be rotated at a relatively high speed about the axis of rotation 102, thereby moving the fluid 110 or 204 through the duct 116. It is done. A broken line 206 in FIG. 2 indicates the position of the cross-sectional view in FIG.

FIG. 3 shows a perspective view of the same cartridge 200.
FIG. 4 shows a perspective sectional view of the cartridge 200 of FIG. FIG. 4 shows a cross-sectional view along line 206. It can be seen that the cartridge 200 is formed of a carrier structure 118 and a cover 400. In this embodiment, there is a hole 402 in the cover 400 for engaging the rotary actuator 404 with the container 106. The container 106 has a first engagement surface 406 and the rotary actuator 404 has a second engagement surface 408. In this embodiment, the second engagement surface 408 is a pin-like structure that bites into the cartridge and contacts the container 106. In some examples, the hole 402 may be larger, and in some examples, the hole 402 may be covered by a seal that can be removed by an operator prior to use. In other examples, the seal covers hole 402 and then second engagement surface 408 can push the seal and contact container 106.

  The container 106 has a small shaft 410 that extends a short distance in the carrier structure 118. This can be used as the first friction element 412 that contacts the second friction element 414 of the carrier structure 118. For example, the shaft 410 can have a press-fit structure or can have some material or surface that will rub when attempting to rotate the container 106 about the axis 102. Alternatively or additionally, the space 416 between the container 106 and the carrier structure 118 can have a structure that is used to increase the rotational friction of the container 106. For example, a small portion of these surfaces may be roughened or may have a structure that prevents free rotation of the container 106 relative to the cartridge 200.

  It can be seen that the carrier structure 118 has a first flat surface 418 formed in the cavity 104. This surface is perpendicular to the axis of rotation 102. It can be seen that the container 106 has a second flat surface 420 that is perpendicular to the axis of rotation 102.

  As an alternative, it is also possible to have a surface that is not perpendicular to the axis of rotation. For example, the friction element may be obtained by a surface that is parallel to the rotation axis or is cylindrically symmetric about the rotation axis. In some examples, the container can have a sidewall or other surface that can contact the cavity. The container can also be supported by bearings or bushings that function as friction elements.

  The surface geometry forming the friction element may also vary. Such surface geometries can have both a vertical component and a parallel component (eg, a 45 ° surface or a concave / convex surface can be used).

  5 to 11 show a method of using the cartridge 200. Initially, the starting position is shown in FIG. Cartridge 200 and container 106 are in the starting position. The rotary actuator 404 is pulled out and is not in contact with the cartridge 200. When the cartridge 200 is rotated, the container 106 rotates with the disk at the same speed.

  Then, in FIG. 6, the rotary actuator 404 has been moved in direction 600 so that the rotary actuator 404, surfaces 406 and 408 are mating with each other. In this particular embodiment, this fixes the position of the container 106 relative to the rotary actuator 404.

  Then, in FIG. 7, the rotary actuator 404 holds the container 106 in a fixed position, and the cartridge 200 is rotated clockwise along the rotation 700. This causes the piercing element 114 to pierce the seal 112 of the fluid reservoir 202. As a result, the fluid 204 leaks and flows into the central cavity 104.

Then, in FIG. 8, the cartridge 200 is rotated counterclockwise in the counterclockwise direction 800 to return the position of the container 106 relative to the rest of the cartridge 200 to its original starting position.
Then, in FIG. 9, the rotary actuator 404 is withdrawn from the cartridge in direction 900. As the rotary actuator 404 moves away from the container, the container 106 is no longer in the fixed position. When the cartridge 200 further rotates, the container 106 rotates in the same manner.

  Next, in FIG. 10, the rotary actuator 404 is pulled out. The cartridge 200 is then rotated and the carrier structure 118 and the container 106 rotate together at the same speed. Arrow 1000 indicates the direction of rotation. This rotation forces fluid 204 out of the perforated fluid reservoir 204 and into the central cavity 104. Further rotation causes fluid 204 to pass through duct 116 and into the fluid structure of cartridge 200.

  FIG. 11 shows the cartridge 200, where all the fluid enters the fluid structure of the cartridge 200 through the duct 116 and the fluid in both the fluid reservoir 204 and the central cavity 104 is empty.

  FIG. 12 shows an alternative design configuration for the cartridge 1200. The design of the cartridge 1200 is similar to the design of the cartridge 100 shown in FIG. 1, but in this embodiment, the container 106 is pierceable seal 112 at both ends located on the surfaces 1202 and 1204, respectively. Have There is a piercing element 114 located near each pierceable seal 112. This particular design configuration can have the advantage that the fluid reservoir 108 is opened at two ends. Thereby, ventilation of the fluid reservoir 108 can be improved and / or drainage from the fluid reservoir 108 can be made more rapid.

  FIG. 13 shows a cartridge 1300 similar to the cartridge 200 shown in FIG. However, in this embodiment, there are pierceable seals 112 on opposite sides 1202 and 1204 on both sides of the side of the container 106. By rotating the container 106 clockwise relative to the carrier structure 118 about the shaft 102, the pierceable seals 112 of both the first fluid reservoir 108 and the second fluid reservoir 202 are pierced simultaneously. This can have the advantage that the first fluid 110 and the second fluid 204 can be mixed within the central cavity 104. Alternatively, the reservoirs may be opened sequentially, in which case one fluid is released first and the second fluid is released in the next step.

14 shows a cross-sectional view of the cartridge 1300 shown in FIG. This view is similar to the top view of cartridge 200.
FIG. 15 shows a portion of the cartridge 1500. In this example, only a small section of the carrier structure with cavities 104 'is shown. In this embodiment, the cavity 104 ′ is disengaged from the rotating shaft 102. The container 106 is designed to slide within the cavity 104 ′ but rotate about the axis of rotation 102. In this embodiment, the container 106 can be rotated about the axis of rotation 102 either clockwise or counterclockwise. There are two different fluid reservoirs 108, 202 that can be opened individually.

  In FIG. 16, the same portion 1500 of the cartridge showing the cavity 104 'is again shown. In this case, the container 106 is rotated clockwise along the rotational direction 1600 relative to the cartridge 1500 around the rotation axis 102. Since the piercing element 114 has opened the pierceable seal 112, the first fluid reservoir 108 has been opened.

  FIG. 17 is similar to FIG. 16 except that the container 106 is rotated counterclockwise in the direction 1700 relative to the cartridge 1500 about the rotation axis 102. In this embodiment, the second fluid reservoir 202 is opened instead.

  FIG. 18 shows a portion of the cartridge 1800 showing the cavity 104 '. The embodiment shown in FIG. 18 is similar to the embodiment shown in FIG. 15 except that the design of the container 106 is different. In this embodiment, a pierceable seal 112 extends below the container 106. As container 106 is rotated relative to cartridge 1800 about the axis of rotation, pierceable seal 112 is pierced or torn by piercing element 114.

  FIG. 19 shows another embodiment of a portion of the cartridge 1900 showing the cavity 104 '. The embodiment shown in FIG. 19 is similar to the embodiment shown in FIG. 15 except that the pierceable seal 112 is at the corner of the container 106 and not at the end. By rotating the container 106 with respect to the cartridge 1900 about the rotation axis, the fluid reservoirs 108 and 202 are also opened.

  FIG. 20 shows a different embodiment of the cartridge with the off-axis container 106. FIG. 20 shows a portion of the cartridge 2000 showing the cavity 104 '. This is not a top view as shown in FIGS. 15 to 19 but a cross-sectional view. The container 106 can be rotated about the axis of rotation and can be moved centrally relative to the cartridge 2000 in either of the directions marked 2002. By moving the cartridge in either direction 2002, the piercing element 114 tears open the pierceable seal 112.

FIG. 21 shows an example of a cartridge 2100 that incorporates the container 1500 and cavity 104 ′ structure 1500 shown in FIG. 15.
FIG. 21 shows a schematic diagram of two embodiments of a cartridge 2100 or test element. The test element 2100 includes a housing 2115 having a substrate or carrier structure 118. In addition to the substrate 118, the disk-shaped test element 2100 typically further includes a cover layer (not shown for clarity). The cover layer can basically carry a fluid structure, but usually only has an opening or a vent opening for delivering a liquid. A central hole or shaft may be provided, around which the test element rotates. The rotation axis 102 is disposed inside the test element in one embodiment, or is disposed outside the test element in another embodiment.

  The housing 2115 of the test element 2100 has a fluidic structure, a microfluidic structure or even a chromatographic structure. Specifically, a sample liquid, which is whole blood, is delivered to the test element 2100 through the sample supply opening 2112. The sample analysis channel 2116 comprises a sample supply opening 2112 at its beginning and a measurement zone 2119 at its end in its flow direction. A channel section 2117 extends between the sample supply opening 2112 and the measurement zone 2119, and the liquid sample flows through the channel section 2117 in a predetermined flow direction to the measurement zone 2119. Transport of the liquid within the test element 2100 is effected by capillary and / or centrifugal forces.

  The flow and / or flow rate of the liquid sample can be influenced by appropriate selection of the fluid structure of the sample analysis channel 2116. For example, in one embodiment, the dimensions of the channel sections 2117, 2118, 2121 are selected to facilitate the generation of capillary forces. In another embodiment, the surface of the channel section is hydrophilized. Also, further flow or filling in individual channel sections of the sample analysis channel 2116 may only be possible after applying an external force, for example a centrifugal force in one embodiment.

  In still other embodiments, different sections of the sample analysis channel 2116 are provided that are sized differently and / or have different functions. For example, in one embodiment, primary channel section 2118 can include a reagent system that reacts with a bodily fluid sample, and in one embodiment, at least one reagent of the reagent system is provided in a dry or lyophilized form. In another embodiment, at least one reagent supplied to the test element 2100 by the fluid reservoir 108 or 202 of the container 106 can also be provided in liquid form.

  The channel section 2117 includes a primary channel section 2118, a capillary stop 2120, and a secondary channel section 2121. The capillary stop 2120 is implemented as a geometric valve in one embodiment, or as a hydrophobic barrier in another embodiment. A secondary channel section 2121 adjacent to the capillary stop 2120 guides the amount of sample that is metered by the capillary stop 2120. The amount flowing through the capillary stop 2120 is controlled by centrifugal force utilizing the rotational speed of the test element 2100.

  At an appropriate rotational speed, separation of red blood cells or other cytoplasmic sample components is initiated in the secondary channel section 2121. Reagents can be included in the reagent system present in channel section 2118, which in one embodiment can be provided in dry form and is already dissolved when the sample liquid enters secondary channel section 2121. Yes. The components of the sample-reagent mixture are captured in collection zone 2122 (plasma collection zone) and collection zone 2123 (red blood cell collection zone) implemented as a chamber.

  A measurement zone or measurement structure 2119 adjacent to the collection zone 2122 has, in one embodiment, a measurement chamber 2124, which in one embodiment includes a porous absorbent matrix. A waste chamber 2125 is arranged behind the measurement chamber 2124 in the flow direction. In one embodiment, after flowing through measurement chamber 2124, reaction participants, sample components, and / or reagent components are discarded into waste chamber 2125.

Waste chamber 2125, in one embodiment, has a fluid connection to measurement zone 2119, such as to receive liquid that has flowed through measurement zone 2119.
In addition, a cleaning liquid source is provided by the container 106. A cleaning liquid channel or duct 2126 is adjacent to the cavity 104 '. A cleaning liquid channel 2126, in one embodiment, is in fluid communication with the measurement zone 2119 at its end so that the cleaning liquid is aspirated through the cleaning liquid channel 2126 and into the measurement chamber 2124. The matrix of the measurement chamber 2124 is washed to remove any extraneous reaction participants that would interfere. The cleaning liquid then reaches the waste chamber 2125 again.

  FIG. 22 shows an embodiment of the automatic analyzer. An automatic analyzer 2200 is adapted to receive the cartridge 200. There is a cartridge spinner 2202 that is operable to rotate the cartridge 200 about the rotation axis 102. A cartridge spinner 2202 has a motor 2204 attached to a gripper 2206 that is attached to a portion of the cartridge 2208. The cartridge 200 is further shown as having a measurement structure or transparent structure 2210. The cartridge 200 can be rotated to move the measurement structure 2210 to the front of the measurement system 2212 so that the measurement system 2212 can perform, for example, optical measurements on the treated biological sample. The rotary actuator 404 shown above is also shown in this figure. The rotary actuator 404 can be used to open one or more fluid reservoirs in the cartridge 200. Actuator 404, cartridge spinner 2202 and measurement system 2212 are all shown connected to hardware interface 2216 of controller 2214. The controller 2214 includes a processor 2218 that connects to a hardware interface 2216, an electronic storage device 2220, an electronic memory 222, and a network interface 2224. Electronic memory 2222 has machine-executable instructions 2230 that allow processor 2218 to control the operation and function of automatic analyzer 2200. Electronic storage device 2220 is shown as including measurements 2232 obtained when instructions 2230 are executed by processor 2218. Network interface 2224 allows processor 2218 to send measurements 2232 to laboratory information system 2228 via network interface 2226.

  FIG. 23 shows a flow chart illustrating a method of operating the automatic analyzer 2200 of FIG. Initially, at step 2300, a biological sample is placed in the fluid structure of cartridge 200. This may be done manually or, if present, by an automated system for dispensing or pipetting to place the biological sample into the cartridge 200. Next, in step 2302, the friction between the cavity and the at least one container is overcome and the pierceable seal is opened by rotating the at least one container relative to the cartridge about the rotation axis 102 of the cartridge 200. In addition, torque is applied to at least one container using the rotary actuator 404. Rotating at least one container relative to the cartridge opens the seal by piercing the pierceable seal with at least one piercing structure. For example, in the embodiment shown in FIG. 22, the actuator 404 is separated from the motor assembly 2202. While the motor 2204 rotates the cartridge 200, the actuator 404 can be used to hold the container in a fixed state. Next, at step 2304, the processor 2218 controls the rotational speed of the cartridge to process the biological sample using the fluid structure into a processed biological sample. Then, at step 2306, the processor controls the rotational speed of the cartridge so that at least one fluid is passed through the duct and at least a portion of the fluid structure. Friction between the cavity and the at least one container causes the at least one container to rotate about the axis of rotation at the same speed as the cartridge. Finally, at step 2308, measurement 2232 is performed using measurement structure 2210 using measurement system 2212. Steps 2302, 2304, and 2306 may be performed in a different order or may be performed multiple times.

DESCRIPTION OF SYMBOLS 100 Cartridge 102 Rotating shaft 104 Central cavity 104 'Cavity 106 Container 108 Fluid reservoir 110 Fluid 112 Punctable seal 114 Puncture element 116 Duct 118 Carrier structure 120 Space for fluid structure 200 Cartridge 202 Second fluid reservoir 204 Second fluid 206 Cross section line 400 Cover 402 Opening 404 Rotary actuator 406 First engagement surface 408 Second engagement surface 410 Shaft 412 First friction element 414 Second friction element 416 Space between container and carrier structure 418 First flat surface 420 Second flat surface 600 direction 700 clockwise rotation 800 counterclockwise rotation 900 direction 1000 rotation direction 1200 cartridge 1202 container surface 1204 container surface 1300 Cartridge 1500 Part of cartridge showing cavity 104 ′ 1600 Counterclockwise rotation 1800 Part of cartridge showing cavity 104 ′ 1900 Part of cartridge showing cavity 104 ′ 2000 Part of cartridge showing cavity 104 ′ 2002 Direction of rotation 2113 Flushing liquid supply Opening 2115 Housing 2116 Sample analysis channel 2117 Channel section 2118 Primary channel section 2119 Measurement zone or structure 2120 Capillary stop 2121 Secondary channel section 2122 Plasma collection zone 2123 Erythrocyte collection zone 2124 Measurement chamber 2125 Waste chamber 2130 Priming structure 2131 Flushing solution Collection chamber 2132 Flash Fluid channel 2133 Valve 2134 Vent channel 2135 Vent opening 2200 Automatic analyzer 2202 Cartridge spinner 2204 Motor 2206 Gripper 2208 Part of cartridge 2210 Measurement structure 2212 Measurement system 2214 Controller 2216 Hardware interface 2218 Processor 2220 Electronic storage device 2222 Electronic memory 2224 Network Interface 2226 Network Connection 2228 Laboratory Information System 2230 Executable Instructions 2232 Measurement 2300 Step of Placing Biological Sample in Fluid Structure 2302 Overcoming the friction between the cavity and at least one container around the axis of rotation of the cartridge Rotating at least one container relative to the cartridge Applying a torque to at least one container using a rotary actuator for the purpose of opening a possible seal 2304 rotational speed of the cartridge so that the biological sample is processed into a processed biological sample using a fluidic structure 2306, controlling the rotational speed of the cartridge so that at least one fluid is allowed to pass through at least a portion of the duct and the fluid structure. 2308: performing a measurement through the measurement structure using the measurement system.

Claims (26)

A method for performing a treated biological treatment measurement using a cartridge (100, 200, 2100) formed from a carrier structure (118) and a cover (400) comprising:
The cartridge is operable to rotate about an axis of rotation (102);
The cartridge further comprises at least one container (106) comprising at least one fluid reservoir (108, 202) comprising at least one fluid (110, 204);
The cartridge comprises cavities (104, 104 ') for each of the at least one container;
The at least one cavity is formed between the carrier structure and the cover;
The at least one container is configured to rotate within the cavity about the axis of rotation of the cartridge;
The at least one container is configured to rotate relative to the cartridge;
Each of the at least one fluid reservoir comprises a pierceable seal (112);
The cavity comprises at least one perforated structure (114) for each of the at least one fluid reservoir;
The at least one piercing structure is configured to open the seal by piercing the pierceable seal when the at least one container is rotated relative to the cartridge;
The at least one container comprises a first friction element (412) and the cavity comprises a second friction element (414);
The first friction element mates with the second friction element;
The first friction element and the second friction element are configured to cause friction between the cavity and the at least one container;
The first at least one container is operable to mate with a second engagement surface (408) of a rotary actuator (404) operable to apply torque to the at least one container. An engagement surface (406),
The cartridge is a fluid structure (120, 2116, 2117, 2118, 2120, 2121, 2122, 2123, 2124, 2125, 2130, 2131, 2132, 2133, 2134) for processing the biological sample into a processed biological sample. 2135),
The fluid structure is formed from the carrier structure and the cover;
The cartridge comprises a duct (116) between the cavity and the fluid structure;
The duct is formed from the carrier structure and the cover;
The fluid structure comprises a measurement structure (2119, 2210) for enabling measurement of the treated biological sample;
The fluid structure is configured to receive the biological sample;
Said method comprises
Placing (2300) the biological sample in the fluidic structure;
To overcome the friction between the cavity and the at least one container and to rotate the at least one container relative to the cartridge about the rotation axis of the cartridge to open the pierceable seal Applying torque to the at least one container using the rotary actuator (2302), wherein rotating the at least one container relative to the cartridge causes the at least one piercing structure to pierce the hole. Opening the seal by drilling a possible seal, (2302);
Controlling the rotational speed of the cartridge to process the biological sample using the fluid structure into the processed biological sample (2304);
Controlling the rotational speed of the cartridge (2306) such that at least one fluid is allowed to pass through the duct and at least a portion of the fluid structure, the friction between the cavity and the at least one container The at least one container rotates about the axis of rotation of the shaft at the same speed as the cartridge; (2306);
Performing a measurement (2308) through the measurement structure using a measurement system;
Including methods. A cartridge (100, 200, 2100) for an automatic analyzer (2200),
The cartridge is formed from a carrier structure (118) and a cover (400);
The cartridge is operable to rotate about an axis of rotation (102);
The cartridge further comprises at least one container (106) comprising at least one fluid reservoir (108, 202) comprising at least one fluid (110, 204);
The cartridge comprises cavities (104, 104 ') for each of the at least one cartridge;
The at least one cavity is formed between the carrier structure and the cover;
The at least one container is configured to rotate within the cavity about the axis of rotation of the cartridge;
The at least one container is configured to rotate relative to the cartridge;
Each of the at least one fluid reservoir comprises a pierceable seal (112);
The cavity comprises at least one perforated structure (114) for each of the at least one fluid reservoir;
The at least one piercing structure is configured to open the seal by piercing the pierceable seal when the at least one container is rotated relative to the cartridge;
The at least one container comprises a first friction element (412) and the cavity comprises a second friction element (414);
The first friction element mates with the second friction element;
The first friction element and the second friction element are configured to cause friction between the cavity and the at least one container;
A first engagement surface that is operable to mate with a second engagement surface (408) of a rotary actuator that is operable to apply torque to the at least one container; (406)
The cartridge is a fluid structure (120, 2116, 2117, 2118, 2120, 2121, 2122, 2123, 2124, 2125, 2130, 2131, 2132, 2133, 2134) for processing the biological sample into a processed biological sample. 2135),
The fluid structure is formed from the carrier structure and the cover;
The cartridge comprises a duct (116) between the cavity and the fluid structure;
The duct is formed in the carrier structure and the cover;
The fluid structure comprises a measurement structure (2219, 2210) for enabling measurement of the treated biological sample;
A cartridge (100, 200, 2100), wherein the fluidic structure is configured to receive the biological sample.   The cartridge of claim 2, wherein the cartridge comprises a plurality of fluid reservoirs (108, 202).   The cartridge of claim 3, wherein the plurality of fluid reservoirs are operable to be opened at different angular positions of the at least one container relative to the cartridge. The at least one container has a plurality of surfaces (1202, 1204);
The chamber of claim 3 or 4, wherein the pierceable seal for each of the plurality of fluid reservoirs is distributed on two or more of the plurality of surfaces.   The first friction element and the second friction element are a rough surface, a surface having adhesive properties, a series of protrusions, a matching sinusoidal surface, a press-fit structure, a separation structure, and a ratchet structure. The cartridge according to any one of claims 2 to 5, comprising any one. One of the at least one container is a centrally located container (104);
The cartridge according to any one of claims 2 to 6, wherein the rotation shaft passes through the container located at the center. One or more of the at least one container is configured to slide within the cavity;
8. The device according to claim 2, wherein the one or more of the at least one container is configured to rotate about the rotation axis of the cartridge by sliding in the cavity. 9. A cartridge according to claim 1. The carrier structure comprises a disc-shaped portion;
The disc-shaped part has a circular profile;
The circular profile has a center;
The cartridge according to claim 2, wherein the rotation shaft passes through the center. The cartridge comprises an opening (402);
The at least one container is operable to rotate relative to the cartridge through the opening;
The opening exposes the first engagement surface;
The cartridge of claim 9, wherein the first engagement surface and the second engagement surface are configured to mechanically mate.   The cartridge of claim 10, wherein the opening is sealed using a cover layer.   10. A cartridge according to any one of claims 2 to 9, wherein the first engagement surface and the second engagement surface are configured to magnetically mate.   The cartridge according to any one of claims 2 to 12, wherein the at least one container is a plurality of containers.   14. A cartridge according to any one of claims 2 to 13, wherein the measurement structure is a transparent structure (2119) and / or comprises two or more electrodes.   15. A cartridge according to any one of claims 2 to 14, wherein the at least one perforation structure is formed from the carrier structure.   16. A cartridge according to any one of claims 2 to 15, wherein the at least one container is entirely within the cover and the carrier structure.   17. A cartridge according to any one of claims 2 to 16, wherein the carrier structure is disk-shaped. The cavity has a first flat surface;
18. A cartridge according to any one of claims 2 to 17, wherein the container has a second flat surface (420). The first friction element is formed on the first flat surface;
The second friction element is formed on the second flat surface;
19. The first friction element and the second friction element are configured to maintain contact when the at least one container is rotated about the axis of rotation. Cartridge. The first flat surface is perpendicular to the axis of rotation;
20. A cartridge according to claim 18 or 19, wherein the second flat surface is perpendicular to the axis of rotation.   21. The at least one container is constrained to rotate about the axis of rotation so that the first flat surface and the second flat surface maintain a constant distance. The cartridge according to any one of the above.   22. A cartridge according to any one of claims 2 to 21, wherein the piercing structure is configured to pierce the pierceable seal that is perpendicular to the axis of rotation.   23. A cartridge according to any one of claims 2 to 22, wherein the at least one container is constrained to only allow rotational motion about the rotational axis of the cartridge within the cavity. . The at least one container comprises a side wall;
24. A cartridge according to any one of claims 2 to 23, wherein the side wall comprises the pierceable seal.   25. The cartridge of claim 24, wherein the pierceable seal and the axis of rotation form an acute angle. An automatic analyzer configured to receive a cartridge according to any one of claims 2 to 25, comprising:
The automatic analyzer comprises a cartridge spinner (2202), a rotary actuator (404), a measurement system (2212), and a controller (2214) configured to control the automatic analyzer, the control So that an apparatus rotates at least one container relative to the cartridge for the purpose of opening a pierceable seal using the rotary actuator (2302);
Controlling the rotational speed of the cartridge for the purpose of processing a biological sample using a fluid structure by controlling the cartridge spinner to produce a processed biological sample (2304);
To control (2306) the rotational speed of the cartridge for the purpose of allowing at least one fluid to pass through a duct and at least a portion of the fluid structure, and to measure using the measurement structure and the measurement system. As implemented (2308)
Composed,
Automatic analyzer.

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